title: TRIM22 inhibits the TRAF6-stimulated NF-κB pathway by targeting TAB2 for degradation.
abstract: Tripartite motif containing 22 (TRIM22), a member of the TRIM/RBCC family, has been reported to activate the nuclear factor-kappa B (NF-κB) pathway in unstimulated macrophage cell lines, but the detailed mechanisms governing this activation remains unclear. We investigated this mechanism in HEK293T cells. We found that overexpression of TRIM22 could activate the NF-κB pathway and conversely, could inhibit the tumor necrosis factor receptor-associated factor 6 (TRAF6)-stimulated NF-κB pathway in HEK293T cells. Further experiments showed that TRIM22 could decrease the self-ubiquitination of TRAF6, and interact with and degrade transforming growth factor-β activated kinase 1 binding protein 2 (TAB2), and that these effects could be partially rescued by a TRIM22 RING domain deletion mutant. Collectively, our data indicate that overexpression of TRIM22 may negatively regulate the TRAF6-stimulated NF-κB pathway by interacting with and degrading TAB2.
authors.affiliation: Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qiu
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.forename: Han
authors.initials: H
authors.lastname: Xiao
authors.forename: Binlian
authors.initials: B
authors.lastname: Sun
authors.forename: Rongge
authors.initials: R
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D000070584:Tripartite Motif Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015778:Minor Histocompatibility Antigens; D016328:NF-kappa B; D012097:Repressor Proteins; C410585:TAB2 protein, human; D048029:TNF Receptor-Associated Factor 6; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins